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1.
Environ Sci Technol ; 58(22): 9863-9874, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38780413

RESUMO

The long-term leaching of polyfluoroalkyl substances (PFAS) within the vadose zone of an AFFF application site for which the depth to groundwater is approximately 100 m was investigated by characterizing the vertical distribution of PFAS in a high spatial resolution. The great majority (99%) of PFAS mass resides in the upper 3 m of the vadose zone. The depths to which each PFAS migrated, quantified by moment analysis, is an inverse function of molar volume, demonstrating chromatographic separation. The PFAS were operationally categorized into three chain-length groups based on the three general patterns of retention observed. The longest-chain (>∼335 cm3/mol molar volume) PFAS remained within the uppermost section of the core, exhibiting minimal leaching. Conversely, the shortest-chain (<∼220 cm3/mol) PFAS accumulated at the bottom of the interval, which coincides with the onset of a calcic horizon. PFAS with intermediate-chain lengths were distributed along the length of the core, exhibiting differential magnitudes of leaching. The minimal or differential leaching observed for the longest- and intermediate-chain-length PFAS, respectively, demonstrates that retention processes significantly impacted migration. The accumulation of shorter-chain PFAS at the bottom of the core is hypothesized to result from limited deep infiltration and potential-enhanced retention associated with the calcic horizon.


Assuntos
Fluorocarbonos , Água Subterrânea , Poluentes Químicos da Água , Água Subterrânea/química , Monitoramento Ambiental
2.
Opt Express ; 32(3): 2916-2928, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297528

RESUMO

We demonstrate a quantum-enhanced lidar capable of performing confident target detection and rangefinding in the presence of strong, time-varying classical noise whilst operating with over five orders of magnitude separation between signal and background levels and target reflectivities down to -52 dB. We use a log-likelihood-based framework to introduce a new protocol for dynamic background tracking, verifying resilience of our system to both fast- and slow-modulation jamming in regimes where a classical illumination-based system fails to find a target. These results demonstrate the advantage of exploiting quantum correlations for lidar applications, providing a clear route to implementation in real-world scenarios.

3.
Phys Rev Lett ; 131(3): 030602, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37540850

RESUMO

Neutral atoms are a promising platform for scalable quantum computing, however, prior demonstration of high fidelity gates or low-loss readout methods have employed restricted numbers of qubits. Using randomized benchmarking of microwave-driven single-qubit gates, we demonstrate average gate errors of 7(2)×10^{-5} on a 225 site atom array using conventional, destructive readout. We further demonstrate a factor of 1.7 suppression of the primary measurement errors via low-loss, nondestructive, and state-selective readout on 49 sites while achieving gate errors of 2(9)×10^{-4}.

4.
J Biol Chem ; 299(4): 103069, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36841477

RESUMO

Transferases are ubiquitous across all known life. While much work has been done to understand and describe these essential enzymes, there have been minimal efforts to exert tight and reversible control over their activity for various biotechnological applications. Here, we apply a rational, computation-guided methodology to design and test a transferase-class enzyme allosterically regulated by light-oxygen-voltage 2 sensing domain. We utilize computational techniques to determine the intrinsic allosteric networks within N-acyltransferase (Orf11/∗Dbv8) and identify potential allosteric sites on the protein's surface. We insert light-oxygen-voltage 2 sensing domain at the predicted allosteric site, exerting reversible control over enzymatic activity. We demonstrate blue-light regulation of N-acyltransferase (Orf11/∗Dbv8) function. Our study for the first time demonstrates optogenetic regulation of a transferase-class enzyme as a proof-of-concept for controllable transferase design. This successful design opens the door for many future applications in metabolic engineering and cellular programming.


Assuntos
Aciltransferases , Proteínas Recombinantes de Fusão , Aciltransferases/química , Aciltransferases/genética , Regulação Alostérica , Sítio Alostérico , Luz , Oxigênio , Domínios Proteicos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Ativação Enzimática/efeitos da radiação
5.
Phys Rev Lett ; 129(20): 200501, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36461988

RESUMO

We demonstrate a native CNOT gate between two individually addressed neutral atoms based on electromagnetically induced transparency. This protocol utilizes the strong long-range interactions of Rydberg states to enable conditional state transfer on the target qubit when operated in the blockade regime. An advantage of this scheme is it enables implementation of multiqubit CNOT^{k} gates using a pulse sequence independent of qubit number, providing a simple gate for efficient implementation of digital quantum algorithms and stabilizer measurements for quantum error correction. We achieve a loss corrected gate fidelity of F_{CNOT}^{cor}=0.82(6), and prepare an entangled Bell state with F_{Bell}^{cor}=0.66(5), limited at present by laser power. We present a number of technical improvements to advance this to a level required for fault-tolerant scaling.

6.
Tree Physiol ; 42(1): 130-144, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34302175

RESUMO

Current carbon cycle models attribute rising atmospheric CO2 as the major driver of the increased terrestrial carbon sink, but with substantial uncertainties. The photosynthetic response of trees to elevated atmospheric CO2 is a necessary step, but not the only one, for sustaining the terrestrial carbon uptake, but can vary diurnally, seasonally and with duration of CO2 exposure. Hence, we sought to quantify the photosynthetic response of the canopy-dominant species, Quercus robur, in a mature deciduous forest to elevated CO2 (eCO2) (+150 µmol mol-1 CO2) over the first 3 years of a long-term free air CO2 enrichment facility at the Birmingham Institute of Forest Research in central England (BIFoR FACE). Over 3000 measurements of leaf gas exchange and related biochemical parameters were conducted in the upper canopy to assess the diurnal and seasonal responses of photosynthesis during the 2nd and 3rd year of eCO2 exposure. Measurements of photosynthetic capacity via biochemical parameters, derived from CO2 response curves, (Vcmax and Jmax) together with leaf nitrogen concentrations from the pre-treatment year to the 3rd year of eCO2 exposure, were examined. We hypothesized an initial enhancement in light-saturated net photosynthetic rates (Asat) with CO2 enrichment of ≈37% based on theory but also expected photosynthetic capacity would fall over the duration of the study. Over the 3-year period, Asat of upper-canopy leaves was 33 ± 8% higher (mean and standard error) in trees grown in eCO2 compared with ambient CO2 (aCO2), and photosynthetic enhancement decreased with decreasing light. There were no significant effects of CO2 treatment on Vcmax or Jmax, nor leaf nitrogen. Our results suggest that mature Q. robur may exhibit a sustained, positive response to eCO2 without photosynthetic downregulation, suggesting that, with adequate nutrients, there will be sustained enhancement in C assimilated by these mature trees. Further research will be required to understand the location and role of the additionally assimilated carbon.


Assuntos
Dióxido de Carbono , Quercus , Dióxido de Carbono/fisiologia , Florestas , Fotossíntese/fisiologia , Folhas de Planta , Árvores/fisiologia
7.
Vet J ; 274: 105707, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34148015

RESUMO

Blastomycosis is a prominent fungal disease in the United States. Vitamin D status has been found to be altered in critical illness and various infectious diseases. The objectives of this study were to compare serum 25-hydroxyvitamin D (25[OH]D) concentrations in dogs with blastomycosis and healthy controls, to assess the change in serum 25(OH)D concentrations in dogs with blastomycosis after 30 days of treatment, and to determine if baseline serum 25(OH)D concentrations in dogs with blastomycosis were associated with in-hospital, 30-day, or end-of-study mortality. In this prospective cohort study, 19 dogs newly diagnosed with blastomycosis had serum 25(OH)D concentrations measured with a commercially available validated radioimmunoassay at the time of diagnosis and 30 days after start of treatment. These values were compared to 24 healthy control dogs. Serum 25(OH)D concentrations at the time of diagnosis were lower in dogs with blastomycosis (median, 203 nmol/L; range, 31-590 nmol/L) than in clinically healthy control dogs (259.5 nmol/L, 97-829 nmol/L; P = 0.01). Despite clinical improvement, there was no significant change in serum 25(OH)D concentrations from baseline to 30-day follow-up. Dogs with baseline serum 25(OH)D concentrations <180.5nmol/L had a greater odds of death during hospitalization (odds ratio [OR], 15.0; 95% confidence interval [CI], 1.4-191.3; P = 0.04) and at 30 days follow-up (OR, 30.0; 95% CI, 2.5-366.7; P = 0.006). These findings highlight the need for further studies evaluating the prognostic value of vitamin D status in dogs with blastomycosis at diagnosis and throughout treatment and remission.


Assuntos
Antifúngicos/uso terapêutico , Blastomicose/veterinária , Doenças do Cão/sangue , Vitamina D/análogos & derivados , Animais , Blastomyces/isolamento & purificação , Blastomicose/sangue , Blastomicose/tratamento farmacológico , Blastomicose/mortalidade , Estudos de Coortes , Doenças do Cão/tratamento farmacológico , Doenças do Cão/mortalidade , Cães , Feminino , Masculino , Estudos Prospectivos , Vitamina D/sangue
9.
Sci Rep ; 9(1): 6628, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036834

RESUMO

Metagenomic analysis is a highly promising technique in paleogenetic research that allows analysis of the complete genomic make-up of a sample. This technique has successfully been employed to archaeological sediments, but possible leaching of DNA through the sequence limits interpretation. We applied this technique to the analysis of ancient DNA (aDNA) from Late Quaternary stalagmites from two caves in Western Georgia, Melouri Cave and Solkota. Stalagmites form closed systems, limiting the effect of leaching, and can be securely dated with U-series. The analyses of the sequence data from the Melouri Cave stalagmite revealed potential contamination and low preservation of DNA. However, the two Solkota stalagmites preserved ancient DNA molecules of mammals (bear, roe deer, bats) and plants (chestnut, hazelnut, flax). The aDNA bearing layers from one of the two Solkota stalagmites were dated to between ~84 ka and ~56 ka BP by U-series. The second Solkota stalagmite contained excessive detrital clay obstructing U-series dating, but it also contained bear bones with a minimum age of ~50 BP uncalibrated years and ancient DNA molecules. The preservation of authentic ancient DNA molecules in Late Quaternary speleothems opens up a new paleogenetic archive for archaeological, paleontological and paleoenvironmental research.


Assuntos
DNA Antigo , DNA de Plantas/genética , Mamíferos/genética , Animais , Georgia , Paleontologia
10.
J Dairy Sci ; 101(12): 11170-11174, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30243623

RESUMO

Many cull dairy cows enter the marketing system and travel to widely dispersed and specialized slaughter plants, and they may experience multiple handling events (e.g., loading, unloading, mixing), change of ownership among dealers, and feed and water deprivation during transport and at livestock markets. The objectives of this study were to describe the diverse management of cull dairy cows in Canada and establish consensus on ways to achieve improvements. A 2-day expert consultation meeting was convened, involving farmers, veterinarians, regulators, and experts in animal transport, livestock auction, and slaughter. The 15 participants, recruited from across Canada, discussed regional management practices for cull cattle, related risk factors, animal welfare problems, and recommendations. An audio recording of the meeting was used to extract descriptive data on cull cattle management and identify points of agreement. Eight consensus points were reached: (1) to assemble information on travel times and delays from farm to slaughter; (2) to increase awareness among producers and herd veterinarians of potential travel distances and delays; (3) to promote pro-active culling; (4) to improve the ability of personnel to assess animal condition before loading; (5) to identify local options for slaughter of cull dairy cows; (6) to investigate different management options such as emergency slaughter and mobile slaughter; (7) to ensure that all farms and auctions have, or can access, personnel trained and equipped for euthanasia; and (8) to promote cooperation among enforcement agencies and wider adoption of beneficial regulatory options.


Assuntos
Bem-Estar do Animal , Bovinos/fisiologia , Meios de Transporte , Animais , Canadá , Consenso , Indústria de Laticínios , Fazendeiros , Fazendas , Feminino , Políticas , Encaminhamento e Consulta
11.
BMC Geriatr ; 17(1): 264, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29132301

RESUMO

BACKGROUND: The objectives of this study were to determine: 1) the prevalence of frailty using Fried's phenotype method and the Short Performance Physical Battery (SPPB), 2) agreement between frailty assessment methods, 3) the feasibility of assessing frailty using Fried's phenotype method and the SPPB. METHODS: This cross-sectional study was conducted at a geriatric out-patient clinic in Hamilton, Canada. A research assistant conducted all frailty assessments. Patients were classified as non-frail, pre-frail or frail according to Fried's phenotype method and the SPPB. Agreement among methods is reported using the Cohen kappa statistic (standard error). Feasibility data included the percent of eligible participants agreeing to attempt the frailty assessments (criterion for feasibility: ≥90% of patients agreeing to the frailty assessment), equipment required, and safety considerations. A p-value of <0.05 is considered significant. RESULTS: A total of 110 participants (92%) and 109 participants (91%) agreed to attempt Fried's phenotype method and SPPB, respectively. No adverse events occurred during any assessments. According to Fried's phenotype method, the prevalence of frailty and pre-frailty was 35% and 56%, respectively, and according to the SPPB, the prevalence of frailty and pre-frailty was 50% and 35%, respectively. There was fair to moderate agreement between methods for determining which participants were frail (0.488 [0.082], p < 0.001) and pre-frail (0.272 [0.084], p = 0.002). CONCLUSIONS: Frailty and pre-frailty are common in this geriatric outpatient population, and there is fair to moderate agreement between Fried's phenotype method and the SPPB. Over 90% of the patients who were eligible for the study agreed to attempt the frailty assessments, demonstrating that according to our feasibility criteria, frailty can be assessed in this patient population. Assessing frailty may help clinicians identify high-risk patients and tailor interventions based on baseline frailty characteristics.


Assuntos
Idoso Fragilizado , Fragilidade/diagnóstico , Avaliação Geriátrica/métodos , Serviços de Saúde para Idosos/normas , Ambulatório Hospitalar/normas , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Fragilidade/epidemiologia , Humanos , Masculino
12.
Rev Sci Instrum ; 87(7): 073107, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27475548

RESUMO

We present a pair of optimized objective lenses with long working distances of 117 mm and 65 mm, respectively, that offer diffraction limited performance for both Cs and Rb wavelengths when imaging through standard vacuum windows. The designs utilise standard catalog lens elements to provide a simple and cost-effective solution. Objective 1 provides NA = 0.175 offering 3 µm resolution whilst objective 2 is optimized for high collection efficiency with NA = 0.29 and 1.8 µm resolution. This flexible design can be further extended for use at shorter wavelengths by simply re-optimising the lens separations.

13.
Equine Vet J ; 48(1): 33-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25256702

RESUMO

REASONS FOR PERFORMING STUDY: To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. OBJECTIVES: To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). STUDY DESIGN: Observer-blinded, placebo-controlled trial. METHODS: Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20). Observation of postural and event behaviours was undertaken at 2 pretreatment time points followed by 4 post treatment time points, using scan (instantaneous) and focal sampling. RESULTS: In comparison to pretreatment baselines, donkeys receiving meloxicam were more alert post treatment than the placebo group. They were observed lying down less frequently (P = 0.007), with their eyes closed less frequently (P = 0.04) and having a high head carriage more frequently (P = 0.02). Dozing behaviour decreased after meloxicam compared with the pretreatment baseline (P = 0.03). Donkeys given meloxicam also showed more interest in their environment, turning to look at environmental stimuli more frequently (P = 0.05) than those in the placebo group post treatment. Neither the meloxicam nor the placebo group showed a significant post treatment improvement in lameness scores. CONCLUSIONS: Working donkeys receiving meloxicam were more active and alert compared with their pretreatment behaviour, confirming the potential value of nonsteroidal anti-inflammatory drugs in identifying behaviours indicative of pain in working donkeys. Behavioural assessment of pain in working donkeys in field clinic conditions will enable veterinary staff and owners to identify welfare issues promptly and monitor response to analgesia. The Summary is available in Chinese--see Supporting information.


Assuntos
Analgésicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Equidae , Tiazinas/farmacologia , Tiazóis/farmacologia , Animais , Feminino , Masculino , Meloxicam
14.
Int J Clin Pract ; 69(12): 1457-64, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26422446

RESUMO

BACKGROUND: In 2014 the UK National Institute for Health and Care Excellence recommended reducing the threshold for offering statin therapy to patients from a 10-year modelled risk of cardiovascular disease (CVD) of 20% to 10%. AIM: To describe the response of patients in UK primary care with a CVD risk between 10% and 20% to an invitation to attend a consultation to discuss statins. DESIGN AND SETTING: Review of electronic medical records at one GP practice in the East of England. METHOD: We invited all patients who had attended an NHS Health Check at the practice, had a QRisk(®) score between 10% and 20%, and were not prescribed statins to attend designated clinics in the practice to discuss starting statins. We reviewed the medical records to identify those who had attended the clinics and those who had chosen to start a statin. RESULTS: Of 410 patients invited, 100 (24.4%) patients attended the designated clinics and 45 (11%) chose to start a statin. Those who chose to start a statin were older and with a higher QRisk(®) than those who did not. Among those who attended, individuals who started a statin had a higher QRisk(®) than those who did not and were more likely to be current or ex-smokers. CONCLUSIONS: The proportion choosing to start a statin was substantially lower than previously estimated. Large population-based studies with long-term follow-up are needed to assess the impact on health and workload of this change in guidance.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Inglaterra , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Medição de Risco
15.
Vet Rec Open ; 2(1): e000105, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26392903

RESUMO

INTRODUCTIONS: Working donkeys are at risk of developing multiple, acute and chronic health problems. The ability to recognise and assess pain in donkeys associated with these health problems is important for people responsible for their care and treatment, including owners and veterinary or animal health workers. AIMS AND OBJECTIVES: The aims of this study were firstly to quantify the prevalence of a range of clinical abnormalities within a sample of working donkeys; and secondly to find out whether these abnormalities were associated with potential behavioural indicators of pain. MATERIALS AND METHODS: One hundred and thirty-three entire male adult working donkeys were observed for ten minutes before and after a one-hour rest period. Using an ethogram developed and refined in associated studies, posture and event behaviours were recorded by a single observer. The health of each donkey was then assessed by a veterinarian for specific clinical abnormalities. RESULTS: Working donkeys have a high prevalence of clinical abnormalities and a number of behaviours are associated with these. Significant associations were found between observed behaviours and systemic, ocular and limb-related clinical abnormalities. Cumulative clinical scores for limb-related problems were associated with a higher frequency of leg trembling, knuckling of the forelimb, leg-lifting and weight-shifting behaviours (all R≥0.4; P<0.001) and with a lower frequency of weight-bearing evenly on all four feet (R=-0.458; P<0.001). CONCLUSIONS: The specific behaviour changes associated with clinical abnormalities identified in this study, together with general changes in demeanour identified in related studies, may be useful in assessing the presence and severity of pain in working donkeys and their response to medical and palliative interventions.

16.
Can Commun Dis Rep ; 41(4): 69-72, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29769935

RESUMO

In December 2014, the first detection in Canada of a highly pathogenic avian influenza A (HPAI) virus was reported in poultry within the Fraser Health Authority of British Columbia. It was the second outbreak of HPAI from Eurasian H5 reassortment viruses in North America. The Fraser Health Authority provided the lead public health coordination for this response as well as consultation and support to the occupational health response. The public health response focused on contact tracing, monitoring and follow-up for household, farm worker and other community contacts exposed on the affected farms. A total of 50 contacts were identified. Contacts received daily active monitoring by public health nurses for seven days from their last exposure and were advised to self-monitor until day 10. All contacts and other household members were recommended seasonal influenza vaccination to protect against further possible reassortment with human influenza viruses circulating within the community at the time. A total of 26 (52%) contacts were recommended chemoprophylaxis for ongoing exposure to the affected barns and flocks, of whom only 11 (42%) initiated this. During the seven-day active surveillance period, four contacts developed acute respiratory symptoms and influenza B was identified in one individual. Local area health care providers and acute care facilities were alerted to the outbreak and public messaging was provided regarding the human health risks from avian influenza. Collaboration between health and agriculture at the local, regional, provincial and federal levels was key to a rapid response to this outbreak.

17.
Equine Vet J ; 46(6): 771-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24433378

RESUMO

REASONS FOR PERFORMING THE STUDY: Lameness is prevalent in working donkeys and has major welfare implications; however, a detailed study of the associated clinical signs is lacking. OBJECTIVES: To describe the range and prevalence of clinical signs and conformation associated with lameness in working draught donkeys. STUDY DESIGN: Prospective, cross-sectional, observational study. METHODS: Data were collected from 102 working draught donkeys in Pakistan. A lameness assessment adapted for working donkeys was used to record clinical signs of lameness, gait, limb conformation and pain responses in the feet, limbs and spine using observation, palpation and manipulation. Lameness at the walk was scored from 0 to 10 (sound to nonweightbearing). RESULTS: Every donkey examined had gait abnormalities, with 5% having a nonweightbearing limb. Lameness was significantly more severe with older age, lower body condition score and forward-at-the-knee conformation. More severe lameness was also associated with pain responses in the hoof walls, palpation of limb joints and spinal flexion. Joint, tendon and foot pathology was highly prevalent, as well as pain responses to joint flexion and spinal manipulation. Conformational abnormalities showed lateral asymmetries. CONCLUSIONS: Over 98% of the world's 42.2 million donkeys are in low-income countries, most being used for work. The high prevalence of lameness, pain and multiple limb and spinal abnormalities in working donkeys is of great welfare concern and highlights the complexity of addressing this problem. This standardised lameness assessment can be used when implementing and monitoring interventions to reduce lameness prevalence in working donkeys.


Assuntos
Equidae , Coxeadura Animal/epidemiologia , Animais , Coxeadura Animal/diagnóstico , Coxeadura Animal/etiologia , Paquistão/epidemiologia
18.
Phys Rev Lett ; 110(10): 103001, 2013 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-23521254

RESUMO

We use a microwave field to control the quantum state of optical photons stored in a cold atomic cloud. The photons are stored in highly excited collective states (Rydberg polaritons) enabling both fast qubit rotations and control of photon-photon interactions. Through the collective read-out of these pseudospin rotations it is shown that the microwave field modifies the long-range interactions between polaritons. This technique provides a powerful interface between the microwave and optical domains, with applications in quantum simulations of spin liquids, quantum metrology and quantum networks.


Assuntos
Modelos Teóricos , Óptica e Fotônica/métodos , Fônons , Fótons , Micro-Ondas , Óptica e Fotônica/instrumentação , Teoria Quântica
19.
Bioanalysis ; 5(4): 403-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23414372

RESUMO

This report gives a summary of the key points raised during a roundtable discussion convened at the American Association of Pharmaceutical Scientists 2012 Annual Meeting and Exposition held in Chicago on 17 October 2012. The science of ADME continues to grow, as does the impact of these studies on drug development. Understanding ADME requires efforts from several scientific specialties. With reductions in pharmaceutical company R&D staff there has been a corresponding growth in CROs with the capabilities and expertise to perform ADME work. This roundtable explored the challenges inherent in understanding ADME and the issues that arise when ADME studies shift from in-house study directors to external scientists working within the business model of a CRO. Pharmaceutical industry scientists and procurement specialists can satisfy their expectations by awareness of the growing expertise within CROs and the need for open communication among all partners involved in outsourced work.


Assuntos
Descoberta de Drogas/métodos , Indústria Farmacêutica/métodos , Serviços Terceirizados/métodos , Humanos
20.
Bone ; 54(1): 76-82, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23356988

RESUMO

PURPOSE: The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. METHODS: Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 µm(2)) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student's t-test for normally distributed data and Mann-Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. RESULTS: Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5]years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4]years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98]wt.% Ca versus 19.40 [1.07]wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99-4.12]wt.% Ca versus 3.95 [0.71]wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97]wt.% Ca for type 2 diabetes versus 20.44 [1.30]wt.% Ca for controls, p=0.121). CONCLUSION: The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes.


Assuntos
Calcificação Fisiológica/fisiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Osteoartrite/complicações , Osteoartrite/fisiopatologia , Adulto , Idoso , Densidade Óssea/fisiologia , Cálcio/metabolismo , Estudos de Casos e Controles , Feminino , Colo do Fêmur/ultraestrutura , Humanos , Masculino , Padrões de Referência
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